Biological psychiatry global open science最新文献

{"title":"Effects of Shared and Nonshared Schizophrenia and Bipolar Disorder Alleles on Cognition and Educational Attainment in the UK Biobank","authors":"Alexander L. Richards ,&nbsp;Eilidh Fenner ,&nbsp;Nicholas E. Clifton ,&nbsp;Darren Cameron ,&nbsp;Claire E. Tume ,&nbsp;Nicholas J. Bray ,&nbsp;Sophie E. Legge ,&nbsp;James T.R. Walters ,&nbsp;Peter A. Holmans ,&nbsp;Michael C. O’Donovan ,&nbsp;Michael J. Owen","doi":"10.1016/j.bpsgos.2025.100601","DOIUrl":"10.1016/j.bpsgos.2025.100601","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment is typically more severe in schizophrenia (SZ) than bipolar disorder (BD). We explored the underlying genetics and biology of this difference and its relationship to educational attainment (EA) using genomic structural equation modeling.</div></div><div><h3>Methods</h3><div>Shared and differentiating fractions of liability for SZ and BD were derived and tested for their association with general intelligence (<em>n</em> = 93,541), fluid intelligence (<em>n</em> = 160,465), and EA (<em>n</em> = 354,609) in the UK Biobank. Liabilities were tested for enrichment in genes with high expression specificity (HES) for developmental stages, cell types, and functional categories.</div></div><div><h3>Results</h3><div>Shared liability was associated with poorer cognition but higher EA. The SZ differentiating fraction (SZ_diff) was associated with poorer cognition and lower EA. When we adjusted for cognition, the effects of SZ_diff on EA were attenuated but still significant. The differentiating fraction was enriched for HES genes for young adulthood (20–30 years), mid-adulthood (30–60 years), and the dentate gyrus.</div></div><div><h3>Conclusions</h3><div>Shared liability for SZ and BD is enriched for alleles that confer risk for poorer cognitive function in the general population but is associated with noncognitive traits that enhance EA. In contrast, SZ_diff is enriched for alleles that confer risk for poorer EA through both cognitive and noncognitive mechanisms, which has implications for interventions. The enrichment of the differentiating fraction for HES genes in early and mid-adulthood and in the dentate gyrus highlights developmental stages and cell types important for future research.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100601"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White Matter Regional Volumes in Relation to Menstrual Cycle Phase and Premenstrual Dysphoric Disorder","authors":"Elin Stenhammar ,&nbsp;Manon Dubol ,&nbsp;Louise Stiernman ,&nbsp;Inger Sundström-Poromaa ,&nbsp;Marie Bixo ,&nbsp;Erika Comasco","doi":"10.1016/j.bpsgos.2025.100573","DOIUrl":"10.1016/j.bpsgos.2025.100573","url":null,"abstract":"<div><h3>Background</h3><div>Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating, and hormone-related mental disorder. Recent evidence suggests alterations in white matter structure during the symptomatic luteal phase in PMDD. In this study, white matter volumes (WMVs) in the brains of women with PMDD versus control women were compared across the menstrual cycle, to determine whether these differences reflect state- or trait-like characteristics.</div></div><div><h3>Methods</h3><div>Anatomical magnetic resonance imaging was performed during the midfollicular phase and the late luteal phase of the menstrual cycle in 28 women with PMDD and 27 control women. WMVs were assessed using voxel-based morphometry, employing both region-of-interest (ROI) and exploratory whole-brain approaches.</div></div><div><h3>Results</h3><div>No group-by-phase interaction effects on WMVs were found. Across menstrual cycle phases, women with PMDD exhibited greater WMVs than control women within ROIs (in the bilateral uncinate fasciculus, right inferior fronto-occipital fasciculus, and left crus and fimbria of the fornix) and across the whole brain (in inferior occipital areas and near the angular gyrus), indicating trait- rather than state-like structural markers of PMDD.</div></div><div><h3>Conclusions</h3><div>These findings suggest that women with PMDD exhibit larger WMVs than healthy control women, during both the symptomatic and asymptomatic phases of the menstrual cycle, in white matter tracts involved in emotion processing and regulation, memory, and connecting limbic and prefrontal regions of relevance to mood disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100573"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased Cerebral Blood Flow in Young Children With Prenatal Alcohol Exposure","authors":"Mohammad Ghasoub ,&nbsp;Madison Long ,&nbsp;Jamie Roeske ,&nbsp;Meaghan V. Perdue ,&nbsp;Xiangyu Long ,&nbsp;Carly McMorris ,&nbsp;Christina Tortorelli ,&nbsp;W. Ben Gibbard ,&nbsp;Catherine Lebel","doi":"10.1016/j.bpsgos.2025.100576","DOIUrl":"10.1016/j.bpsgos.2025.100576","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol exposure during pregnancy can hinder neurodevelopment, causing a range of behavioral and neurological deficits, including structural and functional brain alterations. Moreover, prenatal alcohol exposure (PAE) is associated with cerebral blood flow (CBF) abnormalities in preclinical models. However, it remains unclear to what extent CBF is affected by PAE in humans. In this study, we investigated CBF in young children with PAE.</div></div><div><h3>Methods</h3><div>A total of 171 scans collected from 99 children (35 children [51 scans] with PAE) between the ages of 3 to 8 years were examined. Children underwent a magnetic resonance imaging scan to acquire arterial spin labeling images to quantify CBF. CBF maps were segmented into 110 gray matter regions, and linear mixed models were used to test CBF differences between children with PAE and unexposed children in each region.</div></div><div><h3>Results</h3><div>Children with PAE had decreased CBF compared with unexposed control children, with the largest effects seen in subcortical and medial frontal regions.</div></div><div><h3>Conclusions</h3><div>CBF is negatively altered in children with PAE. CBF reductions may alter nutrient and oxygen delivery to the brain, resulting in impaired neurodevelopment and helping to explain functional deficits seen in PAE. The largest effects were seen in regions associated with cognitive and behavioral functions that are commonly impaired in individuals with PAE. Our findings contribute additional insight into the adverse effects of PAE on neurodevelopment and lay the groundwork for future studies to investigate CBF effects and how they relate to behavior.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100576"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscribers Page","authors":"","doi":"10.1016/S2667-1743(25)00188-0","DOIUrl":"10.1016/S2667-1743(25)00188-0","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100634"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgments","authors":"","doi":"10.1016/j.bpsgos.2025.100630","DOIUrl":"10.1016/j.bpsgos.2025.100630","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100630"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Irritability as a Potentially Causal Risk Pathway to Depression Using Two Genetically Informed Designs","authors":"Amy Shakeshaft ,&nbsp;Olakunle Oginni ,&nbsp;Joanna Martin ,&nbsp;Charlotte A. Dennison ,&nbsp;Olga Eyre ,&nbsp;Ellen Leibenluft ,&nbsp;Sebastian Lundström ,&nbsp;Evie Stergiakouli ,&nbsp;Henrik Larsson ,&nbsp;Paul Lichtenstein ,&nbsp;Argyris Stringaris ,&nbsp;Lucy Riglin ,&nbsp;Mark J. Taylor ,&nbsp;Anita Thapar","doi":"10.1016/j.bpsgos.2025.100566","DOIUrl":"10.1016/j.bpsgos.2025.100566","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is heterogeneous, with diverse risk pathways leading to illness. Identifying causal routes to depression helps prioritize targets for early intervention and prevention strategies. Although irritability is associated with risk for later depression, this association could be explained by confounders, including genetic confounders.</div></div><div><h3>Methods</h3><div>We used two genetically informed designs to examine whether irritability is causally linked to depression. First, using data from the Child and Adolescent Twin Study in Sweden (CATSS) (<em>N</em> = 16,495) and linked Swedish National Patient Register (NPR), we assessed the relationship between irritability and MDD using the monozygotic twin differences design, which controls for genetic influences. Irritability was assessed at age 15 using the Strengths and Difficulties Questionnaire. MDD diagnoses were identified from ages 15 to 25 years using the NPR. Second, we conducted bidirectional two-sample Mendelian randomization (MR) to examine relationships between genetic liability to self-reported irritability and depression, using published genome-wide association studies.</div></div><div><h3>Results</h3><div>In CATSS, associations were observed between irritability at age 15 (parent-reported odds ratio [OR] = 1.93 [1.61–2.34], <em>p</em> = 4.65 × 10⁻¹²; self-reported OR = 1.62 [1.36–1.93], <em>p</em> = 7.13 × 10⁻⁸) and NPR-recorded MDD diagnoses from 15 to 25 years. Monozygotic twin analysis revealed an association between self-reported twin differences in irritability and MDD discordance (OR = 1.57 [1.04–2.36], <em>p</em> = .032). Results were inconclusive for parent-reported irritability (OR = 1.20 [0.73–1.96], <em>p</em> = .47). MR revealed a bidirectional relationship (irritability to depression inverse-variance weighted [IVW] OR = 3.31 [2.07–5.28], <em>p</em> = 5.5 × 10⁻⁷; depression to irritability IVW OR = 1.07 [1.05–1.10], <em>p</em> = 3.2 × 10⁻¹¹).</div></div><div><h3>Conclusions</h3><div>These results indicate that self-reported irritability may represent a causal risk pathway to MDD and thus could serve as a potential target for MDD prevention or early intervention.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100566"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychometric Considerations in Assessing Fear Generalization as a Predictor of Anxiety","authors":"Yannik Stegmann ,&nbsp;Mario Reutter ,&nbsp;Katharina Hutterer ,&nbsp;Lea Hildebrandt ,&nbsp;Jürgen Deckert ,&nbsp;Lorenz Deserno ,&nbsp;Katharina Domschke ,&nbsp;Tina B. Lonsdorf ,&nbsp;Paul Pauli ,&nbsp;Andreas Reif ,&nbsp;Karoline Rosenkranz ,&nbsp;Miriam A. Schiele ,&nbsp;Dirk Schümann ,&nbsp;Peter Zwanzger ,&nbsp;Marta Andreatta ,&nbsp;Matthias Gamer","doi":"10.1016/j.bpsgos.2025.100570","DOIUrl":"10.1016/j.bpsgos.2025.100570","url":null,"abstract":"<div><h3>Background</h3><div>The ability to adaptively transfer acquired fear to novel situations is fundamental for survival in ever-changing environments and may contribute to the emergence and persistence of anxiety disorders. Consequently, research has focused on the assessment of fear generalization profiles to predict individual differences in anxiety. However, substantial heterogeneity in the operationalization of generalization hampers comparisons across studies and poses a risk to the replicability of findings.</div></div><div><h3>Methods</h3><div>To address these issues, we reviewed the literature to identify commonly used methods for characterizing perceptual fear generalization profiles. Then, we conducted simulation analyses to examine correlations between indices and probe their robustness against measurement noise. Finally, we used 2 large empirical datasets (<em>N</em> = 1175 and <em>N</em> = 256 healthy humans) to examine the reliability of these indices and their validity in predicting anxiety-related traits.</div></div><div><h3>Results</h3><div>All identified indices were substantially correlated but highly sensitive to measurement noise, with only minimal differences between methods. Reliabilities were moderate for subjective ratings but poor for skin conductance responses. All indices of fear generalization were unrelated to anxiety-related traits.</div></div><div><h3>Conclusions</h3><div>Overall, a more comprehensive discussion of conceptual and methodological issues is needed to enable informed decisions about how to reliably and validly estimate fear generalization and its relationship with anxiety-related traits or clinical symptoms.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100570"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic and Structural Brain Aging and Their Associations With Major Depressive Disorder","authors":"Eileen Y. Xu ,&nbsp;Claire Green ,&nbsp;Daniel L. McCartney ,&nbsp;Laura K.M. Han ,&nbsp;Kathryn L. Evans ,&nbsp;Rosie M. Walker ,&nbsp;Danni A. Gadd ,&nbsp;Douglas Steele ,&nbsp;Gordon Waiter ,&nbsp;Archie Campbell ,&nbsp;Stephen M. Lawrie ,&nbsp;James H. Cole ,&nbsp;Andrew M. McIntosh ,&nbsp;Xueyi Shen ,&nbsp;Heather C. Whalley","doi":"10.1016/j.bpsgos.2025.100577","DOIUrl":"10.1016/j.bpsgos.2025.100577","url":null,"abstract":"<div><h3>Background</h3><div>A growing body of evidence suggests that major depressive disorder (MDD) may be associated with premature biological aging. However, most studies reported to date have examined brain-based (BrainAge) and DNA methylation (DNAm)–based measures (DNAmAge) of biological age (BioAge) in isolation.</div></div><div><h3>Methods</h3><div>We investigated 2 well-studied BioAge measures in lifetime and current MDD: BrainAge and DNAmAge (4 separate DNAmAge measures based on Horvath, Hannum, GrimAge, and PhenoAge clocks). We used cross-sectional cohort data from GS:STRADL (Generation Scotland: STratifying Resilience and Depression Longitudinally) (BrainAge <em>n</em> = 833; DNAmAge <em>n</em> = 587; age range 26–76 years) and used UK Biobank (UKB) data to test for replication of BrainAge associations with MDD (BrainAge <em>n</em> = 12,018, age range 45–80 years). Premature brain and DNAm aging were operationalized as predicted age difference (PAD), and analyses controlled for age, sex, smoking, and alcohol intake. We also tested individual and additive associations of brain- and DNAm-based PADs to lifetime/current MDD using logistic regression.</div></div><div><h3>Results</h3><div>Individuals with lifetime MDD showed significantly higher BrainAge and DNAmAge in GS, ranging from 1.60 to 2.45 years, than individuals without MDD for all measures except for Horvath age. No differences were found for BrainAge in the UKB. In terms of PAD, lifetime MDD was significantly associated with GrimAge-PAD, PhenoAge-PAD, and Brain-PAD, ranging from odds ratio (OR) = 1.21−1.30 (and in UKB, Brain-PAD OR = 1.05). DNAm-PAD and Brain-PAD demonstrated shared and distinctive associations with lifetime MDD, where PhenoAge-PAD plus Brain-PAD explained maximum variance (area under the curve = 0.69, <em>R</em>² = 9%). No significant associations were found for current MDD.</div></div><div><h3>Conclusions</h3><div>Our findings highlight shared and distinct associations of premature brain and DNAm aging in lifetime MDD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100577"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the Locus Coeruleus in Response to Threat in Anxiety Disorders and Posttraumatic Stress Disorder: An Ultra-High-Field 7T Functional Magnetic Resonance Imaging Study","authors":"Sarah C. Boukezzi ,&nbsp;Philipp T. Neukam ,&nbsp;Nicholas Balderston ,&nbsp;Yael Jacob ,&nbsp;Derek A. Smith ,&nbsp;Yolanda Whitaker ,&nbsp;Sarah B. Rutter ,&nbsp;Vicki Soogrim ,&nbsp;Adriana Feder ,&nbsp;Dennis S. Charney ,&nbsp;Christian Grillon ,&nbsp;Prantik Kundu ,&nbsp;Priti Balchandani ,&nbsp;Laurel S. Morris ,&nbsp;James W. Murrough","doi":"10.1016/j.bpsgos.2025.100596","DOIUrl":"10.1016/j.bpsgos.2025.100596","url":null,"abstract":"<div><h3>Background</h3><div>By harnessing the enhanced spatial resolution and signal power of high-field 7T magnetic resonance imaging (MRI), we assessed the functional involvement of the locus coeruleus (LC), together with the broader threat circuitry, in anxious arousal among individuals with anxiety disorders and posttraumatic stress disorder (PTSD).</div></div><div><h3>Methods</h3><div>Sixty-nine individuals with and without anxiety disorders or PTSD completed a modified no (N), predictable (P), and unpredictable (U) (NPU) threat task during a 7T functional MRI scan. Anxious arousal was measured using the Mood and Anxiety Symptom Questionnaire anxious arousal subscale. Individual data-driven LC segmentations were derived from ultra-high-resolution magnetization transfer contrast scans. We conducted LC functional activation and whole-brain data analyses during the NPU task using both transdiagnostic (Research Domain Criteria–based) and categorical (DSM-5–based) approaches.</div></div><div><h3>Results</h3><div>Greater LC activation during unpredictable threat was positively correlated with anxious arousal across all participants. In whole-brain analyses, the posterior cingulate cortex/precuneus and the subgenual anterior cingulate cortex were significantly activated during unpredictable threat, whereas the posterior insula was significantly activated during predictable threat. Greater activation within key structures of the threat circuitry, including the brainstem, the left hippocampus/amygdala, and the insula was positively correlated with anxious arousal across conditions and participants.</div></div><div><h3>Conclusions</h3><div>This translational and dimensional work advances our understanding of the role of the LC system and threat circuitry in pathological anxiety. Using 7T MRI, this study highlights the functional role of the LC in processing unpredictable threat in association with anxious arousal in individuals with anxiety disorders and PTSD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100596"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Neural Activities and Neuroplasticity Related to Nonpharmacological Interventions for Major Depressive Disorder: A Systematic Literature Review","authors":"Sandeep Vaishnavi ,&nbsp;Alex Leow ,&nbsp;Veronica Nguyen ,&nbsp;Chip Meyer ,&nbsp;Madeline Rose Keleher ,&nbsp;Caroline Leitschuh ,&nbsp;Tarolyn Carlton","doi":"10.1016/j.bpsgos.2025.100572","DOIUrl":"10.1016/j.bpsgos.2025.100572","url":null,"abstract":"<div><div>People with major depressive disorder (MDD) can have impaired neuroplasticity. Antidepressant treatment and some nonpharmacological interventions can lead to changes in neuroplasticity that improve MDD symptoms. However, there are no recent systematic literature reviews (SLRs) on the effect of nonpharmacological interventions for MDD on neuroplasticity. Therefore, we conducted an SLR of articles with primary results published between January 1, 2013, and December 6, 2023, that included adults with depression or MDD (MDD used to refer to both) treated with nonpharmacological products that are U.S. Food and Drug Administration (FDA) cleared and indicated for MDD or are investigative and need FDA review and clearance for use outside of clinical trials. From the 1257 records screened, 101 studies with 4746 participants were included. Electroconvulsive therapy was the most common treatment (used by 46.5% of the studies), followed by repetitive transcranial magnetic stimulation (35.6%). Of the 54 studies that included a healthy control comparison group, 42 (77.8%) found brain differences at baseline between the MDD group and the control group. Most of the studies (95 studies; 94.1%) found statistically significant functional or structural changes in the brain following nonpharmacological treatment for MDD. Of the 74 studies that investigated whether there was a relationship between changes in the brain and improvement in MDD symptoms, 53 (71.6%) found that changes in neuroplasticity corresponded with improvement in depression symptoms. This SLR shows that nonpharmacological interventions for MDD lead to changes in neuroplasticity, which correspond with improvement in MDD symptoms.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100572"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}